Flavin-dependent N-hydroxylating enzymes: Distribution and application

Carolin Mügge, Thomas Heine, Alvaro Gomez Baraibar, Willem J.H. van Berkel, Caroline E. Paul, Dirk Tischler

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Abstract

Amino groups derived from naturally abundant amino acids or (di)amines can be used as “shuttles” in nature for oxygen transfer to provide intermediates or products comprising N-O functional groups such as N-hydroxy, oxazine, isoxazolidine, nitro, nitrone, oxime, C-, S-, or N-nitroso, and azoxy units. To this end, molecular oxygen is activated by flavin, heme, or metal cofactor-containing enzymes and transferred to initially obtain N-hydroxy compounds, which can be further functionalized. In this review, we focus on flavin-dependent N-hydroxylating enzymes, which play a major role in the production of secondary metabolites, such as siderophores or antimicrobial agents. Flavoprotein monooxygenases of higher organisms (among others, in humans) can interact with nitrogen-bearing secondary metabolites or are relevant with respect to detoxification metabolism and are thus of importance to understand potential medical applications. Many enzymes that catalyze N-hydroxylation reactions have specific substrate scopes and others are rather relaxed. The subsequent conversion towards various N-O or N-N comprising molecules is also described. Overall, flavin-dependent N-hydroxylating enzymes can accept amines, diamines, amino acids, amino sugars, and amino aromatic compounds and thus provide access to versatile families of compounds containing the N-O motif. Natural roles as well as synthetic applications are highlighted.• N-O and N-N comprising natural and (semi)synthetic products are highlighted.• Flavin-based NMOs with respect to mechanism, structure, and phylogeny are reviewed.• Applications in natural product formation and synthetic approaches are provided. [Figure not available: see fulltext.].

Original languageEnglish
Pages (from-to)6481-6499
Number of pages19
JournalApplied Microbiology and Biotechnology
Volume104
Issue number15
DOIs
Publication statusPublished - Aug 2020

Keywords

  • Bioactive compounds
  • Biocatalysis
  • Biotransformation
  • Flavoproteins
  • Monooxygenases
  • N-Hydroxylases
  • Phylogenetics
  • Siderophores

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    Mügge, C., Heine, T., Baraibar, A. G., van Berkel, W. J. H., Paul, C. E., & Tischler, D. (2020). Flavin-dependent N-hydroxylating enzymes: Distribution and application. Applied Microbiology and Biotechnology, 104(15), 6481-6499. https://doi.org/10.1007/s00253-020-10705-w